Skip to main content

Advertisement

SpringerLink
Log in

Differentiation capacity of dental pulp stem cell into inner ear hair cell using an in vitro assay: a preliminary step toward treating sensorineural hearing loss

  • Otology
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Purpose

Sensorineural hearing loss (SNHL) is commonly caused by the death or dysfunction of cochlear cell types as a result of their lack of regenerative capacity. However, regenerative medicine, such as stem cell therapy, has become a promising tool to cure many diseases, including hearing loss. In this study, we determined whether DPSCs could differentiate into cochlear hair cell in vitro.

Methods

DPSCs derived from human third molar dental pulp were induced into NSCs using a medium containing basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) for 7 days, and then into cochlear hair cell using a medium containing EGF and IGF-1 for the next 14 days. We used the neuroepithelial protein marker nestin and cochlear hair cell marker myosin VIIa as the markers for cells differentiation. Cells expressing the positive markers under the microscope were confirmed to have differentiated into cochlear hair cell.

Results

DPSCs were successfully induced to differentiate into NSCs, with mean 24% nestin-positive cells. We found that DPSC-derived NSCs have a great capacity in differentiating into inner ear hair cell-like cells with an average of 81% cells presenting myosin VIIa. Thus, DPSCs have high potential to serve as a good resource for SNHL treatment.

Conclusion

We found the high potential of DPSCs to differentiate into NSC. The ability of DPSCs in differentiating into neural lineage cell made them a good candidate for regenerative therapy in neural diseases, such as SNHL

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Rivolta MN (2010) Stem cells and cell lines from the human auditory organ: applications, hurdles and bottlenecks in the development of regenerative therapies for deafness. Drug Discov Today 15(7/8):283–286

    Article  Google Scholar 

  2. Hu Z, Ulfendahl M (2004) The potential of stem cells for the restoration of auditory function in humans. Regen Med 8(3):309–318

    Article  Google Scholar 

  3. Coleman B, Hardman J, Coco A, Epp S, de Silva M, Crook J et al (2006) Fate of embryonic stem cells transplanted into the deafened mammalian cochlea. Cell Transpl 15:369–380

    Article  CAS  Google Scholar 

  4. Parker MA, Corliss DA, Gray B, Anderson JK, Bobbin RP, Snyder EY, Cotanche DA (2007) Neural stem cells injected into the sound-damaged cochlea migrate throughout the cochlea and express markers of hair cells, supporting cells, and spiral ganglion cells. Hear Res 232(1–2):29–43

    Article  Google Scholar 

  5. Cho YB, Cho HH, Jang S, Jeong HS, Park JS (2011) Transplantation of neural differentiated human mesenchymal stem cells into the cochlea of an auditory-neuropathy guinea pig model. Cell Ther Organ Transplant 26:492–498

    CAS  Google Scholar 

  6. Qin H, Zhao LD, Sun JH, Ren LL, Gou WW, Liu HZ et al (2011) The differentiation of mesenchymal stem cells into inner ear hair cell-like cells in vitro. Acta Otolaryngol 131:1136–1141

    Article  CAS  Google Scholar 

  7. Ying W, Min-min D, Hai-bo Y, Sonh-tao G (2007) In vitro differentiation of adipose-derived stem cells into hair cell-like cells in guinea pigs. J Otol 2(2):97–100

    Article  Google Scholar 

  8. Li H, Roblin G, Liu H, Heller S (2003) Generation of hair cells by stepwise differentiation of embryonic stem cells . Proc Natl Acad Sci 100:13495–13500

    Article  CAS  Google Scholar 

  9. Doyle KL, Kazda A, Hort Y, Mckay SM, Oleskevich S (2007) Differentiation of adult mouse olfactory precursor cells into hair cell in vitro. Stem Cells 25:621–627

    Article  CAS  Google Scholar 

  10. Chang CC, Chang KC, Tsai SJ, Chang HH, Lin CP (2014) Neurogenic differentiation of dental pulp stem cells to neuron-like cells in dopaminergic and motor neuronal inductive media. J Formos Med Assoc 113:956–965

    Article  CAS  Google Scholar 

  11. Kawashima N (2012) Characterisation of dental pulp stem cells: a new horizon for tissue regeneration? Arch Oral Biol 57:1439–1458

    Article  Google Scholar 

  12. Dominici M, Blanc KL, Mueller I, Sleper-Conterbach I, Marini F, Krause D et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cell. The international society for cellular therapy position statement. Cytotherapy 8(4):315–317

    Article  CAS  Google Scholar 

  13. Gronthos S, Mankani M, Brahim J, Robey PG, Shi S (2000) Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Sci USA 97:13625–13630

    Article  CAS  Google Scholar 

  14. Karaoz E, Demircan PC, Saglam O, Aksoy A, Kaymaz F, Duruksu G (2011) Human dental pulp demonstrate better neural and epithelial stem cell properties than bone marrow-derived mesenchymal stem cells. Histochem Cell Biol 136:455–473

    Article  Google Scholar 

  15. Arthur A, Rychkov G, Shi S, Koblar SA, Gronthos S (2008) Adult human dental pulp stem cells differentiate toward functionally active neurons under appropriate environmental cues. Stem Cells 26:1787–1795

    Article  CAS  Google Scholar 

  16. Zhang X, Zhou Y, Li H, Wang R, Yang D, Li B, Cao X, Fu J (2018) Transplanted dental pulp stem cell migrate to injured area and express neural markers in a rat model cerebral ischemia. Cell Physiol Biochem 48:258–266

    Article  Google Scholar 

  17. Alsberg E, Recum HA, Mahoney MJ (2006) Environmental cues to guide stem cell fate decision for tissue engineering application. Expert Opin Biol Ther 6(9):847–866

    Article  CAS  Google Scholar 

  18. Bernal A, Arranz L (2018) Nestin-expressing progenitor cells: function, identity and therapeutic implications. Cel Mol Life Sci 75:2177–2194

    Article  CAS  Google Scholar 

  19. Ito J, Kojima K, Kawaguchi S (2001) Survival of neural stem cells in the cochlea. Acta Otolaryngol 121:140–142

    Article  CAS  Google Scholar 

  20. Lee JH, Kang WK, Seo JH, Choi MY, Lee YH, Kim HM, Park KH (2012) Neural differentiation of bone marrow-derived mesenchymal stem cells: applicability for inner ear therapy. Korean Audiol Soc 16:47–53

    Article  Google Scholar 

  21. Mahmoidain-sani MR, Hashemzadeh-chalashtori M, Jami MS, Saidijam M (2017) In vitro differentiation of human bone marrow mesenchymal stem cells to hair cells using growth factors. Int Tinnitus J 21(2):179–184

    Google Scholar 

  22. Pacey LKK, Stead S, Gleave JA, Tomezyk K, Doering LC (2006) Neural stem cell culture: neurosphere generation, microscopical analysis and cryopreservation. Nat Protoc 1:215–222

    Article  Google Scholar 

  23. Devarajan K, Staecker H, Detamore MS (2011) A review of gene delivery and stem cell based therapies for regenerating inner ear hair cells. J Funct Biomater 2:249–270

    Article  CAS  Google Scholar 

  24. Potdar PD, Jethmalani YD (2015) Human dental pulp stem cells: applications in future regenerative medicine. World J Stem cells 7(5):839–851

    Article  Google Scholar 

  25. Appler JM, Goodrich LV (2011) Connecting the ear to the brain: molecular mechanism of auditory circuit assembly. Prog Neurobiol 93(4):488–550

    Article  CAS  Google Scholar 

  26. Estrela C, Alencar AH, Kitten GT, Vencio EF, Gava E (2011) Mesenchymal stem cells in the dental tissue: perspectives for tissue regeneration. Braz Dent J 22:91–98

    Article  Google Scholar 

  27. Hildebrand MS, Dahl H-HM, Hardman J, Coleman B, Shephard RK, de Silva MG (2005) Survival of partially differentiated mouse embryonic stem cells in the scala media of the guinea pig cochlea. J Assoc Res Otolaryngol 6:341–345

    Article  Google Scholar 

Download references

Funding

This research was funded by The Prodia Education and Research Institute.

Author information

Authors and Affiliations

  1. Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medicine, Universitas Sumatera Utara, Jl. Dr. Mansyur No 5, Medan, Sumatera Utara, 20155, Indonesia

    Indri Adriztina, Delfitri Munir &  Farhat

  2. Division of Oral Biology, Departement of Biochemistry and Molecular Biology, Faculty of Dentistry, Trisakti University, Jakarta, Indonesia

    Ferry Sandra

  3. Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia

    Muhamad Ichwan

  4. Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia

    Jenny Bashiruddin

  5. Department of Dermatovenerology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia

    Imam Budi Putra

  6. Department of Clinical Pathology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia

    Rosita Juwita Sembiring

  7. Prodia Stemcell Indonesia, Jl. Kramat VII No.11, Jakarta, Indonesia

    Cynthia Retna Sartika, Angliana Chouw & Endah Dianty Pratiwi

Authors
  1. Indri Adriztina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Delfitri Munir
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ferry Sandra
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Muhamad Ichwan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jenny Bashiruddin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Imam Budi Putra
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Farhat
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rosita Juwita Sembiring
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Cynthia Retna Sartika
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Angliana Chouw
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Endah Dianty Pratiwi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Indri Adriztina.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to declare.

Ethical approval

The experiment was approved by the Health Research Ethical Committee of Medical Faculty of Universitas Sumatera Utara, Indonesia (No: 310/TGL/KEPK FK USU-RSUP HAM/2019).

Informed consent

Informed consent was obtained from participant included in this study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Adriztina, I., Munir, D., Sandra, F. et al. Differentiation capacity of dental pulp stem cell into inner ear hair cell using an in vitro assay: a preliminary step toward treating sensorineural hearing loss. Eur Arch Otorhinolaryngol 279, 1805–1812 (2022). https://doi.org/10.1007/s00405-021-06864-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-021-06864-9

Keywords

Search

Navigation